The Animal Core will support research on F. tularensis in mice to develop a vaccine candidate(s) to protect against inhalational tularemia. The work will include active immunization with F. tularensis vaccine candidate antigens. The immune response of female BALB/c mice will be determined by several in vitro tests and the vaccine conditions that yield a high immune response will be used to vaccinate animals prior to aerosol challenge with five F. tularensis strains. Protection from inhalational tularemia will be assessed on the basis of survival and quantitative organ cultures. After immunization of BALB/c and C57BL/6 mice, which differ in their major histocompatibility complexes, with each of four different killed F. tularensis Schu4 preparations and with the F. tularensis live vaccine strain (LVS), the immune response will be determined by several in vitro tests. The mouse strain and those conditions that yielded the best in vitro immune response to F. tularensis will be used to produce F. tularensis-specific polyclonal antibody expression libraries (PCALS). In addition, monospecific polyclonal antibodies directed against vaccine candidate antigens will be produced. Prophylactic and therapeutic efficacy of the PCALs to aerosol challenge with virulent F. tularensis will be performed on BALB/c mice. Urine and respiratory secretions from infected mice will be used to optimize the development of commercial diagnostic assays.